Biased Histamine Signaling Selectively Gates Oral Fat Preference
54 Pages Posted: 4 Apr 2025 Publication Status: Under Review
More...Abstract
Distinct peripheral neural circuits perceive sugar and fat to guide nutritional value-based food preferences. While orosensory experiences also influence meal size, neural mechanisms underlying selective oral fat preference remain unclear. Our whole-brain activity mapping revealed a striking separation of high-fat diet (HFD) and high-sucrose diet-responsive neuronal ensembles within the paraventricular thalamus (PVT). Employing translating ribosome affinity purification, we identified histamine H3 receptor (H3R) as a marker of PVTHFD neurons. Manipulating H3R expression or histaminergic terminals in the PVT specifically affects HFD consumption. Histamine-mediated H3R activation increases PVTHFD neuronal excitability via G12/13 signaling. This histaminergic circuit integrates oral dietary cues from the mesencephalic nucleus of the trigeminal nerve, regulating fat-texture-response. These findings establish a novel role for PVT in gating oral fat preference and identify H3R-G12/13 axis as a potential target for precise fat-consumption control.
Note:
Funding Information: This work was supported by National Natural Science Foundation of China (U21A20418), the National Key R&D Program of China (2021ZD0202803, 2019YFA050880), and Zhejiang Provincial Natural Science Foundation (LD25H090002).
Declaration of Interests: The authors declare no competing interests.
Ethics Approval Statement: All procedures adhered to the guidelines of the Animal Advisory Committee of Zhejiang Chinese Medical University and the US National Institutes of Health Guidelines for the Care and Use of Laboratory Animals. The Animal Advisory Committee of Zhejiang Chinese Medical University approved all procedures (No. 15827).
Suggested Citation: Suggested Citation